Showing 151-200 of 204 Results
Executive Director, Sarafan ChEM-H
BioDr. Elizabeth Ponder joined Stanford ChEM-H in 2014 and is currently the Executive Director of Sarafan ChEM-H and the Stanford Innovative Medicines Accelerator (IMA). Dr. Ponder completed her Ph.D. and postdoctoral training at Stanford University in the laboratory of Dr. Matthew Bogyo. Her past work has included promoting public-private partnerships in the non-profit sector, managing multidisciplinary research in the higher education sector, and business development consulting in the for-profit biotech sector. Dr. Ponder joined ChEM-H from the University of California, Berkeley where she served as the Executive Director of the Henry Wheeler Center for Emerging & Neglected Diseases (CEND).
Sutardja Chuk Professor of Definitive and Curative Medicine
BioDr. Porteus was raised in California and was a local graduate of Gunn High School before completing A.B. degree in “History and Science” at Harvard University where he graduated Magna Cum Laude and wrote an thesis entitled “Safe or Dangerous Chimeras: The recombinant DNA controversy as a conflict between differing socially constructed interpretations of recombinant DNA technology.” He then returned to the area and completed his combined MD, PhD at Stanford Medical School with his PhD focused on understanding the molecular basis of mammalian forebrain development with his PhD thesis entitled “Isolation and Characterization of TES-1/DLX-2: A Novel Homeobox Gene Expressed During Mammalian Forebrain Development.” After completion of his dual degree program, he was an intern and resident in Pediatrics at Boston Children’s Hospital and then completed his Pediatric Hematology/Oncology fellowship in the combined Boston Chidlren’s Hospital/Dana Farber Cancer Institute program. For his fellowship and post-doctoral research he worked with Dr. David Baltimore at MIT and CalTech where he began his studies in developing homologous recombination as a strategy to correct disease causing mutations in stem cells as definitive and curative therapy for children with genetic diseases of the blood, particularly sickle cell disease. Following his training with Dr. Baltimore, he took an independent faculty position at UT Southwestern in the Departments of Pediatrics and Biochemistry before again returning to Stanford in 2010 as an Associate Professor. During this time his work has been the first to demonstrate that gene correction could be achieved in human cells at frequencies that were high enough to potentially cure patients and is considered one of the pioneers and founders of the field of genome editing—a field that now encompasses thousands of labs and several new companies throughout the world. His research program continues to focus on developing genome editing by homologous recombination as curative therapy for children with genetic diseases but also has interests in the clonal dynamics of heterogeneous populations and the use of genome editing to better understand diseases that affect children including infant leukemias and genetic diseases that affect the muscle. Clinically, Dr. Porteus attends at the Lucille Packard Children’s Hospital where he takes care of pediatric patients undergoing hematopoietic stem cell transplantation.
Associate Professor of Radiation Oncology (Radiation Physics)
Current Research and Scholarly InterestsThe Physical Oncology Lab is interested in making a lasting impact on translational cancer research by building novel physical tools and methods.
Lei (Stanley) Qi
Associate Professor of BioengineeringOn Leave from 01/01/2023 To 06/30/2023
BioDr. Lei (Stanley) Qi is Associate Professor of Bioengineering, Sarafan ChEM-H, and a Chan Zuckerberg Biohub Investigator. Dr. Qi is a leading contributor to the development of CRISPR technology for genome engineering. His lab created the first nuclease-deactivated Cas9 (dCas9) for targeted gene regulation in cells. His lab has since invented a series of CRISPR technologies, including CRISPRi and CRISPRa for targeted gene regulation, epigenome editing, LiveFISH for real-time cell imaging, CRISPR-GO for 3D genome manipulation, CasMINI as a compact CRISPR system for gene therapy, hyperCas12a for multi-gene engineering, and CRISPR antivirals aimed at treating broad RNA viruses.
With a broad interest in mammalian synthetic biology, Dr. Qi's lab focuses on epigenome engineering, immune cell engineering, directed evolution, and novel gene therapy. Additionally, they actively investigate the functional role of the human noncoding genome in immunology and neurobiology. Dr. Qi earned his B.S. in Physics and Math from Tsinghua University and Ph.D. in Bioengineering from the University of California, Berkeley. He was a UCSF Systems Biology Fellow. He joined the faculty at Stanford University in 2014.
Professor of Radiology (Molecular Imaging Program at Stanford) and, by courtesy, of Chemistry
Current Research and Scholarly InterestsProbe chemistry and nanotechnology for molecular imaging and diagnostics
Assistant Professor of Biochemistry and of Developmental Biology
BioDr. Rutaganira uses choanoflagellates—the closest living single-celled relatives to animals—to study the origin of animal cell communication. Dr. Rutaganira applies chemical, genetic, and cell biological tools to probe choanoflagellate cell-cell communication, with implications for understanding not only animal cell signaling, but also the origin of multicellularity in animals.
Elaine and John Chambers Professor of Pediatric Cancer and Professor of Genetics
Current Research and Scholarly InterestsWe investigate the mechanisms by which normal cells become tumor cells, and we combine genetics, genomics, and proteomics approaches to investigate the differences between the proliferative response in response to injury and the hyperproliferative phenotype of cancer cells and to identify novel therapeutic targets in cancer cells.
Kathleen M. Sakamoto
Shelagh Galligan Professor in the School of Medicine
Current Research and Scholarly InterestsMy research focuses on the molecular pathways that regulate normal and aberrant blood cell development, including acute leukemia and bone marrow failure syndromes. We are also studying novel drugs for treatment of cancer.
Associate Professor of Biomedical Data Science, of Biochemistry and, by courtesy, of Statistics
Current Research and Scholarly Interestsstatistical computational biology focusing on splicing, cancer and microbes
Juan G. Santiago
Charles Lee Powell Foundation Professor
Current Research and Scholarly Interestshttp://microfluidics.stanford.edu/Projects/Projects.html
Assistant Professor of Genetics
Current Research and Scholarly InterestsWe study the organizing principles of the genome and how these principles regulate cell identity and developmental switches. We combine Biochemistry and Biophysical methods such as NMR and Hydrogen-Deuterium Exchange-MS with Cell Biology, and Genetics to explore genome organization across length and time scales and understand how cells leverage the diverse biophysical properties of chromatin to regulate genome function.
Assistant Professor of Pathology
Current Research and Scholarly InterestsOur lab works at the interface of immunology, cancer biology, and genomics to study cellular and molecular mechanisms of the immune response to cancer. In particular, we are leveraging high-throughput genomic technologies to understand the dynamics of the tumor-specific T cell response to cancer antigens and immunotherapies (checkpoint blockade, CAR-T cells, and others). We are also interested in understanding the impact of immuno-editing on the heterogeneity and clonal evolution of cancer.
We previously developed genome sequencing technologies that enable epigenetic studies in primary human immune cells from patients: 1) 3D enhancer-promoter interaction profiling (Nat Genet, 2017), 2) paired epigenome and T cell receptor (TCR) profiling in single cells (Nat Med, 2018), 3) paired epigenome and CRISPR profiling in single cells (Cell, 2019), and high-throughput single-cell ATAC-seq in droplets (Nature Biotech, 2019). We used these tools to study fundamental principles of the T cell response to cancer immunotherapy (PD-1 blockade) directly in cancer patient samples (Nature Biotech, 2019; Nat Med, 2019).
Associate Professor of Chemical Engineering
BioPlants have an extraordinary capacity to harvest atmospheric CO2 and sunlight for the production of energy-rich biopolymers, clinically used drugs, and other biologically active small molecules. The metabolic pathways that produce these compounds are key to developing sustainable biofuel feedstocks, protecting crops from pathogens, and discovering new natural-product based therapeutics for human disease. These applications motivate us to find new ways to elucidate and engineer plant metabolism. We use a multidisciplinary approach combining chemistry, enzymology, genetics, and metabolomics to tackle problems that include new methods for delignification of lignocellulosic biomass and the engineering of plant antibiotic biosynthesis.
Professor of Psychiatry and Behavioral Sciences (Major Laboratories and Clinical Translational Neurosciences Incubator), of Neurobiology and, by courtesy, of Obstetrics and Gynecology
Current Research and Scholarly InterestsWe study how our brains generate social interactions that differ between the sexes. Such gender differences in behavior are regulated by sex hormones, experience, and social cues. Accordingly, we are characterizing how these internal and external factors control gene expression and neuronal physiology in the two sexes to generate behavior. We are also interested in understanding how such sex differences in the healthy brain translate to sex differences in many neuro-psychiatric illnesses.
Virginia and D. K. Ludwig Professor
Current Research and Scholarly InterestsA basic question in developmental biology involves the mechanisms used to generate the three-dimensional organization of a cell from a one-dimensional genetic code. Our goal is to define these mechanisms using both molecular genetics and biochemistry.
Naima G. Sharaf
Assistant Professor of Biology and, by courtesy, of Structural Biology
Current Research and Scholarly InterestsResearch in the lab bridges biology, microbiology, and immunology to translate lipoprotein research into therapeutics
Sapp Family Provostial Professor, The Catherine Holman Johnson Director of Stanford Bio-X and Professor of Biology and of Neurobiology
Current Research and Scholarly InterestsThe goal of research in the Shatz Laboratory is to discover how brain circuits are tuned up by experience during critical periods of development both before and after birth by elucidating cellular and molecular mechanisms that transform early fetal and neonatal brain circuits into mature connections. To discover mechanistic underpinnings of circuit tuning, the lab has conducted functional screens for genes regulated by neural activity and studied their function for vision, learning and memory.
Head of Medicinal Chemistry
BioDr. Mark Smith joined Stanford ChEM-H in May 2013 as the Head of the Medicinal Chemistry Knowledge Center. He graduated with a Ph.D. from the laboratory of Prof. Richard Stoodley at the University of Manchester Institute for Science and Technology (UMIST), where his research focused on the application of Lewis acid catalyzed hetero Diels-Alder reactions to the synthesis of novel disaccharide structures. In 2000, Dr. Smith joined the research laboratory of Prof. David Crich at the University of Illinois at Chicago. Here his research focused on the generation of new reagents for the synthesis of beta-mannosides from thioglycosides. From 2002 to 2013, Dr. Smith worked as a medicinal chemist in Roche’s research facilities both in Palo Alto, CA and then Nutley, NJ, where he specialized in antiviral research.
Hyongsok Tom Soh
Professor of Radiology (Early Detection), of Electrical Engineering, of Bioengineering and, by courtesy, of Chemical Engineering
BioDr. Soh received his B.S. with a double major in Mechanical Engineering and Materials Science with Distinction from Cornell University and his Ph.D. in Electrical Engineering from Stanford University. From 1999 to 2003, Dr. Soh served as the technical manager of MEMS Device Research Group at Bell Laboratories and Agere Systems. He was a faculty member at UCSB before joining Stanford in 2015. His current research interests are in analytical biotechnology, especially in high-throughput screening, directed evolution, and integrated biosensors.
Edward I. Solomon
Monroe E. Spaght Professor of Chemistry and Professor of Photon ScienceOn Leave from 04/01/2023 To 06/30/2023
Current Research and Scholarly InterestsProf. Solomon's work spans physical-inorganic, bioinorganic, and theoretical-inorganic chemistry, focusing on spectroscopic elucidation of the electronic structure of transition metal complexes and its contribution to reactivity. He has advanced our understanding of metal sites involved in electron transfer, copper sites involved in O2 binding, activation and reduction to water, structure/function correlations over non-heme iron enzymes, and correlation of biological to heterogeneous catalysis.
Associate Director, High-Throughput Screening, Innovative Medicines Accelerator (IMA)
Current Role at StanfordAssociate Director, High-Throughput Screening Knowledge Center, , Sarafan ChEM-H and Innovative Medicine Accelerator (IMA)
This high-throughput screening (HTS) laboratory allows Stanford researchers and others to discover novel modulators of targets that otherwise would not be practical in industry. The center incorporates instrumentation (purchased with NCRR NIH Instrumentation grant numbers S10RR019513, S10RR026338, S10OD025004, and S10OD026899), databases, compound libraries, and personnel whose previous sole domains were in industry.
Among our instrumentation are a fully automated Molecular Devices ImageXpress Micro Confocal High-Content fluorescence microplate imager, with live cell, fluidics and phase contrast options, an Echo 655 Acoustic Dispense, a Thermo integrated HTS robotic system, a Caliper Life Sciences SciClone ALH3000 and an Agilent Bravo microplate liquid handler, and the BMG Clariostarplus, Tecan Infinite M1000 and M1000 PRO and Molecular Devices FlexStation II 384 fluorescence, luminescence and absorbance multimode microplate readers.
We have over 180,000 small molecules for compound screens, 15,000 cDNAs for genomic screens, and whole genome siRNA libraries targeting the human genome (the siARRAY whole human genome siRNA library from Dharmacon, targeting 21,000 human genes) and the mouse genome (Qiagen mouse whole genome siRNA set V1 against 22,124 genes).
The HTSKC main screening lab is located in ChEM-H W008, the cell-based assay development lab is located in CCSR Room 0133-North Wing, between the Transgenic Mouse Facility, and the Stanford Genomics Facility.
Aaron F. Straight
Pfeiffer and Herold Families Professor, Professor of Biochemistry and, by courtesy, of Chemical and Systems Biology
Current Research and Scholarly InterestsWe study the biology of chromosomes. Our research is focused on understanding how chromosomal domains are specialized for unique functions in chromosome segregation, cell division and cell differentiation. We are particularly interested in the genetic and epigenetic processes that govern vertebrate centromere function, in the organization of the genome in the eukaryotic nucleus and in the roles of RNAs in the regulation of chromosome structure.
Katrin J Svensson
Assistant Professor of Pathology
Current Research and Scholarly InterestsMolecular metabolism
Cell biology and function
James H. Clark Professor in the School of Engineering and Professor of Chemical Engineering and of BioengineeringOn Leave from 10/01/2022 To 06/30/2023
Current Research and Scholarly InterestsProgram Overview
The world we enjoy, including the oxygen we breathe, has been beneficially created by biological systems. Consequently, we believe that innovative biotechnologies can also serve to help correct a natural world that non-natural technologies have pushed out of balance. We must work together to provide a sustainable world system capable of equitably improving the lives of over 10 billion people.
Toward that objective, our program focuses on human health as well as planet health. To address particularly difficult challenges, we seek to synergistically combine: 1) the design and evolution of complex protein-based nanoparticles and enzymatic systems with 2) innovative, uniquely capable cell-free production technologies.
To advance human health we focus on: a) achieving the 120 year-old dream of producing “magic bullets”; smart nanoparticles that deliver therapeutics or genetic therapies only to specific cells in our bodies; b) precisely designing and efficiently producing vaccines that mimic viruses to stimulate safe and protective immune responses; and c) providing a rapid point-of-care liquid biopsy that will count and harvest circulating tumor cells.
To address planet health we are pursuing biotechnologies to: a) inexpensively use atmospheric CO2 to produce commodity biochemicals as the basis for a new carbon negative chemical industry, and b) mitigate the intermittency challenges of photovoltaic and wind produced electricity by producing hydrogen either from biomass sugars or directly from sunlight.
More than 25 years ago, Professor Swartz began his pioneering work to develop cell-free biotechnologies. The new ability to precisely focus biological systems toward efficiently addressing new, “non-natural” objectives has proven tremendously useful as we seek to address the crucial and very difficult challenges listed above. Another critical feature of the program is the courage (or naivete) to approach important objectives that require the development and integration of several necessary-but- not-sufficient technology advances.
Associate Professor of Mechanical Engineering, Senior Fellow at the Woods Institute for the Environment and Professor, by courtesy, of Radiology (Precision Health and Integrated Diagnostics)
Current Research and Scholarly InterestsThe long-term goal of Dr. Tang's research program is to harness mass transport in microfluidic systems to accelerate precision medicine and material design for a future with better health and environmental sustainability.
Current research areas include: (I) Physics of droplets in microfluidic systems, (II) Interfacial mass transport and self-assembly, and (III) Applications in food allergy, single-cell wound repair, and the bottom-up construction of synthetic cell and tissues in close collaboration with clinicians and biochemists at the Stanford School of Medicine, UCSF, and University of Michigan.
For details see https://web.stanford.edu/group/tanglab/
Hawa Racine Thiam
Assistant Professor of Bioengineering and of Microbiology and Immunology
Current Research and Scholarly InterestsCellular Biophysical Mechanisms of Innate Immune Cells Functions
Professor of Genetics, of Biology and, by courtesy, of Chemistry
Current Research and Scholarly InterestsWe develop chemogenetic and optogenetic technologies for probing and manipulating protein networks, cellular RNA, and the function of mitochondria and the mammalian brain. Our technologies draw from protein engineering, directed evolution, chemical biology, organic synthesis, high-resolution microscopy, genetics, and computational design.
Professor of Photon Science and of Structural Biology
Current Research and Scholarly InterestsUbiquitin signaling: structure, function, and therapeutics
Ubiquitin is a small protein modifier that is ubiquitously produced in the cells and takes part in the regulation of a wide range of cellular activities such as gene transcription and protein turnover. The key to the diversity of the ubiquitin roles in cells is that it is capable of interacting with other cellular proteins either as a single molecule or as different types of chains. Ubiquitin chains are produced through polymerization of ubiquitin molecules via any of their seven internal lysine residues or the N-terminal methionine residue. Covalent interaction of ubiquitin with other proteins is known as ubiquitination which is carried out through an enzymatic cascade composed of the ubiquitin-activating (E1), ubiquitin-conjugating (E2), and ubiquitin ligase (E3) enzymes. The ubiquitin signals are decoded by the ubiquitin-binding domains (UBDs). These domains often specifically recognize and non-covalently bind to the different ubiquitin species, resulting in distinct signaling outcomes.
We apply a combination of the structural (including protein crystallography, small angle x-ray scattering, cryo-electron microscopy (Cryo-EM) etc.), biocomputational and biochemical techniques to study the ubiquitylation and deubiquitination processes, and recognition of the ubiquitin chains by the proteins harboring ubiquitin-binding domains. Current research interests including SARS-COV2 proteases and their interactions with polyubiquitin chains and ubiquitin pathways in host cell responses, with an ultimate goal of providing strategies for effective therapeutics with reduced levels of side effects.
Protein self-assembly processes and applications.
The Surface layers (S-layers) are crystalline protein coats surrounding microbial cells. S-layer proteins (SLPs) regulate their extracellular, self-assembly by crystallizing when exposed to an environmental trigger. We have demonstrated that the Caulobacter crescentus SLP readily crystallizes into sheets both in vivo and in vitro via a calcium-triggered multistep assembly pathway. Observing crystallization using a time course of Cryo-EM imaging has revealed a crystalline intermediate wherein N-terminal nucleation domains exhibit motional dynamics with respect to rigid lattice-forming crystallization domains. Rate enhancement of protein crystallization by a discrete nucleation domain may enable engineering of kinetically controllable self-assembling 2D macromolecular nanomaterials. In particular, this is inspiring designing robust novel platform for nano-scale protein scaffolds for structure-based drug design and nano-bioreactor design for the carbon-cycling enzyme pathway enzymes. Current research focuses on development of nano-scaffolds for high throughput in vitro assays and structure determination of small and flexible proteins and their interaction partners using Cryo-EM, and applying them to cancer and anti-viral therapeutics.
Multiscale imaging and technology developments.
Multimodal, multiscale imaging modalities will be developed and integrated to understand how molecular level events of key enzymes and protein network are connected to cellular and multi-cellular functions through intra-cellular organization and interactions of the key machineries in the cell. Larger scale organization of these proteins will be studied by solution X-ray scattering and Cryo-EM. Their spatio-temporal arrangements in the cell organelles, membranes, and cytosol will be further studied by X-ray fluorescence imaging and correlated with cryoEM and super-resolution optical microscopy. We apply these multiscale integrative imaging approaches to biomedical, and environmental and bioenergy research questions with Stanford, DOE national labs, and other domestic and international collaborators.
Taia T. Wang, MD, PhD, MSCI
Assistant Professor of Medicine (Infectious Diseases) and of Microbiology and Immunology
Current Research and Scholarly InterestsLaboratory of Mechanisms in Human Immunity and Disease Pathogenesis
Antibodies are a critical component of host defense. While the importance of humoral immunity has been recognized for decades, substantial gaps in knowledge remain around how antibodies function, and how their function is regulated, in vivo. Our laboratory performs studies designed to fill in these gaps, with the goal of enabling new vaccine and therapeutic strategies to prevent human disease. My interest in this area culminated from training in medicine, RNA virus biology (PhD), and molecular antibody biology (postdoctoral training). The intersection of these topics, viral immunity and disease pathogenesis, is the focus of our work. The essential question driving our research is why a small subset of people develop severe or fatal disease during viral infection while most infections result in a subclinical or mild outcome, even in at-risk populations. Our hypothesis is that the antibody signaling pathways that are engaged during viral infection through Fc gamma receptors (FcγRs) are a key driver of these distinct outcomes. We are focused on several major unknowns to address this hypothesis: How are antibody effector functions regulated in vivo and does this change in disease? How do distinct signaling pathways engaged by IgG immune complex-FcγR interactions impact host cell genetic regulation and the ultimate inflammatory/immune response? What are the tissue-specific functions that antibodies engage? How does the heterogeneity in post-translational modifications (PTMs) of human antibodies contribute to heterogeneity in viral immunity?
Current clinical studies:
An Open Label Study of IgG Fc Glycan Composition in Human Immunity
Principal Investigator: Taia T. Wang, MD, PhD
Robert Eckles Swain Professor of Chemistry and Professor, by courtesy, of Chemical Engineering
BioRobert Eckles Swain Professor in Chemistry Robert Waymouth investigates new catalytic strategies to create useful new molecules, including bioactive polymers, synthetic fuels, and sustainable plastics. In one such breakthrough, Professor Waymouth and Professor Wender developed a new class of gene delivery agents.
Born in 1960 in Warner Robins, Georgia, Robert Waymouth studied chemistry and mathematics at Washington and Lee University in Lexington, Virginia (B.S. and B.A., respectively, both summa cum laude, 1982). He developed an interest in synthetic and mechanistic organometallic chemistry during his doctoral studies in chemistry at the California Institute of Technology under Professor R.H. Grubbs (Ph.D., 1987). His postdoctoral research with Professor Piero Pino at the Institut fur Polymere, ETH Zurich, Switzerland, focused on catalytic hydrogenation with chiral metallocene catalysts. He joined the Stanford University faculty as assistant professor in 1988, becoming full professor in 1997 and in 2000 the Robert Eckles Swain Professor of Chemistry.
Today, the Waymouth Group applies mechanistic principles to develop new concepts in catalysis, with particular focus on the development of organometallic and organic catalysts for the synthesis of complex macromolecular architectures. In organometallic catalysis, the group devised a highly selective alcohol oxidation catalyst that selectively oxidizes unprotected polyols and carbohydrates to alpha-hyroxyketones. In collaboration with Dr. James Hedrick of IBM, we have developed a platform of highly active organic catalysts and continuous flow reactors that provide access to polymer architectures that are difficult to access by conventional approaches.
The Waymouth group has devised selective organocatalytic strategies for the synthesis of functional degradable polymers and oligomers that function as "molecular transporters" to deliver genes, drugs and probes into cells and live animals. These advances led to the joint discovery with the Wender group of a general, safe, and remarkably effective concept for RNA delivery based on a new class of synthetic cationic materials, Charge-Altering Releasable Transporters (CARTs). This technology has been shown to be effective for mRNA based cancer vaccines.
William M. Hume Professor in the School of Medicine, Professor of Structural Biology, of Molecular and Cellular Physiology and of Photon Science
Current Research and Scholarly InterestsOur laboratory studies molecular interactions that underlie the establishment and maintenance of cell and tissue structure. Our principal areas of interest are the architecture and dynamics of intercellular adhesion junctions, signaling pathways that govern cell fate determination, and determinants of cell polarity. Our overall approach is to reconstitute macromolecular assemblies with purified components in order to analyze them using biochemical, biophysical and structural methods.
Francis W. Bergstrom Professor and Professor, by courtesy, of Chemical and Systems Biology
Current Research and Scholarly InterestsMolecular imaging, therapeutics, drug delivery, drug mode of action, synthesis
Albert Y. Wu, MD, PhD, FACS
Assistant Professor of Ophthalmology
Current Research and Scholarly InterestsMy translational research focuses on using autologous stem cells to recreate a patient’s ocular tissues for potential transplantation. We are generating tissue from induced pluripotent stem cells to treat limbal stem cell deficiency in patients who are bilaterally blind. By applying my background in molecular and cellular biology, stem cell biology, oculoplastic surgery, I hope to make regenerative medicine a reality for those suffering from orbital and ocular disease.
Joseph C. Wu, MD, PhD
Director, Stanford Cardiovascular Institute, Simon H. Stertzer, MD, Professor and Professor of Radiology
Current Research and Scholarly InterestsDrug discovery, drug screening, and disease modeling using iPSC.